Abstract
Transplantation with neural stem cells (NSCs) is a promising clinical therapy for Alzheimer’s disease (AD). However, the final fate of grafted NSCs is mainly determined by the host microenvironment. Therefore, this study investigated the role of Sanjiao acupuncture in the NSCs-treated hippocampus of a mouse model, senescence-accelerated mouse prone 8 (SAMP8) using Western blot, real-time fluorescent PCR, and immunofluorescence techniques. Meanwhile, we developed a co-culture model of hippocampal tissue specimens and NSCs in vitro, to observe the effects of acupuncture on survival, proliferation and differentiation of grafted NSCs using flow cytometry. Results showed that acupuncture pre- and post-NSCs transplantation significantly improved senescence-induced cognitive dysfunction (P < 0.05); upregulated the expression of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and brain-derived neurotrophic factor (BDNF) (P < 0.05); and also increased the count of neuron-specific nuclear protein (NeuN)- and glial fibrillary acidic protein (GFAP)-positive cells (P < 0.05). Therapeutic acupuncture may regulate the cytokine levels associated with survival, proliferation, and differentiation of NSCs in hippocampal microenvironment, to promote the repair of damaged cells, resulting in improved cognitive performance in mice.
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Abbreviations
- NSCs:
-
Neural stem cells
- AD:
-
Alzheimer’s disease
- SAMP8:
-
Senescence-accelerated mouse prone 8
- SAMR1:
-
Senescence-accelerated mouse resistance 1
- EGF:
-
Epidermal growth factor
- bFGF:
-
Basic fibroblast growth factor
- NeuN:
-
Neuron-specific nuclear protein
- GFAP:
-
Glial fibrillary acidic protein
- BrdU:
-
Bromodeoxyuridine
- DG:
-
Dentate gyrus
- RC:
-
SAMR1 control group
- PC:
-
SAMP8 control group
- PS:
-
SAMP8 sham operation group
- PT:
-
SAMP8 NSCs transplantation group
- PTA:
-
SAMP8 NSCs transplantation with acupoint group
- PTN:
-
SAMP8 NSCs transplantation with non-acupoint group
- BDNF:
-
Brain-derived neurotrophic factor
- BMP4:
-
Bone morphogenic protein 4
- SDF1:
-
Stromal cell-derived factor 1
- VEGF:
-
Vascular endothelial growth factor
- SNK:
-
Student-Newman-Keuls
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Acknowledgments
This work was funded by National Natural Science Foundation of China (81202740), Specialized Research Fund for the Doctoral Program of Higher Education (20121210120002), Tian** Natural Science Fund (12JCQNJC07400), State-funded Construction Projects-Key Specialized Subject of Clinical Laboratory Medicine (2013-544), and Tian** Public Health Bureau Science and Technology Fund (2014KY15, 2013KG142).
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Lan Zhao and Chunlei Zhou contributed equally to this work.
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Zhao, L., Zhou, C., Li, L. et al. Acupuncture Improves Cerebral Microenvironment in Mice with Alzheimer’s Disease Treated with Hippocampal Neural Stem Cells. Mol Neurobiol 54, 5120–5130 (2017). https://doi.org/10.1007/s12035-016-0054-5
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DOI: https://doi.org/10.1007/s12035-016-0054-5